I have been a registered dietitian for just over 4 years and have spent the last 2 of these years working as part of a team that cares for children with inherited metabolic disorders (IMDs). One of which is called Maple Syrup Urine Disease (MSUD).
MSUD is a life-long genetic disorder of branched-chain amino acid (BCAA) metabolism and is a consequence of insufficient branched-chain α-ketoacid dehydrogenase complex (BCKAD) enzymes.
This means that people with MSUD will quickly accumulate high concentrations of BCAAs (namely leucine, isoleucine, and valine) and their respective branched chain keto acids in the plasma and cerebrospinal fluid if they were to consume a ‘normal’ diet. Leucine and its subsequent keto acid (2 oxo-isocaproic acids) are particularly neurotoxic when present in excessive amounts and if untreated can result in seizures, coma, and death.
In May 2014, MSUD was approved for screening in England on day 5-8 of life as part of the extended newborn screening programme. Nevertheless, many patients can become unwell before a positive screening result is obtained, largely due to drinking leucine-rich breast milk and/or infant formula from birth.
When an infant is well, the dietary management of MSUD from diagnosis until the introduction of solid food is based around regulating the amount of breast milk/infant formula in the diet in a bid to restrict leucine intake. In many cases, breast milk/infant formula is limited to as little as 5oz per day or 1.5g of protein per day to prevent high plasma leucine concentrations. However, consuming such small amounts of breast milk/infant formula will fall short of the total protein, fluid and other nutrients the infant needs.
To ensure this gap is plugged, a BCAA-free infant ‘protein substitute’ is given to supplement the breastmilk/infant formula and provide these deficient nutrients. The amount of BCAA-free infant protein substitute will increase over time as a growing infant subsequently requires more fluid and nutrition as they increase in weight.
Now that we have a greater understanding of an MSUD diet during infancy, the challenges of complementary feeding will become clear. Complementary feeding begins at approximately 4-6 months of age but not before 17 weeks. This process increases the solid food content of the diet whilst gradually reducing the volume of infant/breast milk and BCAA-free infant protein substitute consumed.
Given that the BCAA-free infant protein substitute composes the bulk of an MSUD infant’s nutrition, it is imperative that the decrease in its intake is met with a corresponding increase in a product commonly termed a ‘second stage’ protein substitute. This is usually formulated as a semi-solid and taken off a spoon offering a more concentrated, lower volume version of the BCAA-free infant ‘protein substitute’. Gradually trading one product for the other should maintain good metabolic control and growth.
The introduction of pureed, low protein (and thus low leucine) fruits and vegetables make for a logical first step towards eating solid food. This helps to introduce the infant to a variety of textures whilst theoretically having a negligible impact upon leucine levels. Once low protein solids are consistently consumed at each mealtime, it is likely that the intake of breast milk/infant formula will wane. As a result, plasma leucine levels will start to fall and as such, will indicate the need to start re-introducing leucine into the diet via food.
At this stage, the concept of MSUD leucine ‘exchanges’ is unveiled. Weighing exchanges is a strategy to help parents regulate their infant’s leucine intake when their diet becomes more varied. A single MSUD leucine exchange is calculated by assessing the weight of a particular food that contains 50mg of leucine. There are resources available1 that provide some information, but the leucine content of many foods is unknown.
In these cases, an MSUD leucine exchange is instead equated to the amount of food that contains 0.5g of protein as the protein content is usually indicated on food labelling. The assumption being that on average, 0.5g of protein contains approximately 50mg of leucine2. Over time, the process revolves around removing 1 leucine exchanges worth of breast milk/infant formula and replacing it with 1 leucine exchange from food.
Unfortunately, many foods that are associated with the word ‘protein’ i.e meat, eggs, fish, etc are not allowed in an MSUD diet as they contain far too much leucine/protein per gram of product. Instead of small, weighed amounts of foods such as potatoes and cereals can be utilized for leucine exchanges.
Given the degree of dietary restriction in an MSUD diet, patients can be heavily reliant on special low-protein foods that are available on prescription. An array of artificial low-protein food is available, ranging from biscuits to pasta and pizza bases to burgers, many of which have negligible protein content. Crucially, these products add a sense of normality and variety to an MSUD diet.
I have personal experience of introducing complementary foods in two MSUD patients during my career thus far. It can be a challenging time for parents in a number of ways. Accepting their child will never eat the same diet as the rest of the family can be a big psychological issue. The transition between the first and second stage protein substitutes can be troublesome due to a change of taste, texture, and presentation.
Finally, the maths required, the continual weighing of foods and the fear of making a miscalculation can create a heavy burden. As a dietitian, it is my role to help support, educate and empower parents during this potentially testing time.
The above is intended as a brief overview of complementary feeding in MSUD. There are chapters in books many times the length of this blog dedicated to this topic alone. In summary, complementary feeding in MSUD has all the challenges of regular weaning with a number of additional considerations and potential stresses. I have purposely omitted any discussion around the management of acute illness during this time as I think that is another topic for another day!
1.Genetic Metabolic Dietitians International (2015). Available: https://www.gmdi.org/Resources/Leucine-and-Protein-Content-of-Foods [Accessed: Dec 2018].
2.MacDonald, A, and White, F. (2015) Amino Acid Disorders. in: Clinical Paediatric Dietetics (4th ed) pp. 425. Wiley, Chichester.